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E Ritz

Publications and source records attributed to E Ritz.

At least 181 records · Page 10Linked to original sources
PubMed1999

Hypertrophy of intramyocardial arteriolar smooth muscle cells in experimental renal failure.

Wall thickening of intramyocardial arteries in patients with chronic renal failure may contribute to the increased susceptibility of the uremic heart to ischemic injury. In this context, the following questions arise: (1) Is intramyocardial wall thickening in experimental renal failure due to hypertrophy, hyperplasia or both? (2) Which stimuli trigger wall thickening? Using novel stereologic techniques (Nucleator, Selector), intramyocardial arteries were examined in sham-operated and subtotally nephrectomized (SNX) Sprague Dawley rats with moderate renal failure of 8 wk duration. Systolic BP during the experiment was not significantly different in both groups. Absolute and relative left ventricular weight, wall thickness (5.69 +/- 1.11 microm versus 4.42 +/- 0.99 microm), and wall-to-lumen ratio of intramyocardial arteries (0.117 +/- 0.03 microm/microm versus 0.089 +/- 0.01 microm/microm) were significantly greater in SNX than in sham-operated rats. The mean cell and nuclear volume of intramyocardial arteriolar smooth muscle cells was significantly increased in SNX rats (650 +/- 230 microm3 versus 430 +/- 90 microm3 and 26 +/- 4.5 versus 19.9 +/- 2.2 microm3, respectively). In parallel, the total arteriolar wall volume was significantly greater in the left ventricle of SNX (+58%) compared with sham rats. In contrast, the total length of all left ventricular arteries was comparable in both groups. The increase in mean cell volume without significant change in cell number indicates that arteriolar wall thickening in the heart of SNX rats is explained by hypertrophy rather than hyperplasia of arterial smooth muscle cells. This finding in a nonhypertensive experimental model of chronic renal failure contrasts with findings in spontaneously hypertensive rats. Independent of BP and left ventricular hypertrophy, specific growth signals must act on cardiac arteriolar smooth muscle cells.

Animals↗
PubMed1999

The ET(A) receptor blocker LU 135252 prevents chronic transplant nephropathy in the "Fisher to Lewis" model.

The effect of the orally highly bioavailable and specific endothelin A (ET(A)) receptor antagonist LU 135252 was assessed in a model of chronic renal allograft nephropathy. Kidneys of Fisher rats were orthotopically grafted to Lewis rats. Fisher autografts and kidneys after uninephrectomy served as controls. All animals received low-dose cyclosporin A (CsA; 1.5 mg/kg body wt) for 10 d after surgery. Allotransplanted animals were then randomized to receive standard diet or a diet designed to deliver 30 mg of LU 135252/kg body wt per d for 35 wk. BP was monitored telemetrically. Treatment with LU 135252 did not affect systolic or diastolic pressure. Indices of glomerulosclerosis (GSI), and tubulointerstitial and vascular damage were measured. Chronic transplant nephropathy was almost completely prevented by LU 135252 compared with untreated allografts or kidneys of uninephrectomized controls, i.e., GSI 0.7 +/- 0.12 versus 1.6 +/- 0.25 (P < 0.001) versus 0.7 +/- 0.06 (P < 0.001). Allograft weight and serum creatinine were significantly lower in treated versus untreated animals. The results are consistent with the notion that ET(A) receptor-mediated events play a role in the genesis of chronic transplant nephropathy.

Animals↗
PubMed1999

Angiotensin II receptor type 1 gene expression in human glomerulonephritis and diabetes mellitus.

The renin-angiotensin system plays an important role in the progression of chronic renal disease. Although the expression of renin and angiotensin-converting enzyme in experimental and human renal disease has been well characterized, no information is available regarding human angiotensin type 1 (AT1) receptor expression. The net effect of renin depends on AT1 receptor expression, among other factors. Receptor expression was determined in renal biopsy samples (including all tissue components) and isolated glomeruli from patients with glomerulonephritis (GN) or diabetic nephropathy (non-insulin-dependent diabetes mellitus). Biopsy samples and isolated glomeruli from tumor-free tissue from tumor nephrectomies served as controls. Human AT1 receptor gene expression was determined by quantitative reverse transcription-PCR, using an AT1 receptor deletion mutant as the internal standard. In whole biopsy samples from 37 patients with various types of GN, AT1 receptor mRNA levels were lower, compared with nine control biopsy samples (P < 0.001). AT1 receptor mRNA levels were also significantly lower (P < 0.001) in eight samples from patients with diabetic nephropathy. In microdissected glomeruli, AT1 receptor gene expression was significantly lower in samples from patients (n = 22) with various types of GN, compared with 12 microdissected tumor nephrectomy control samples (P < 0.0023). It is concluded that AT1 receptor mRNA expression is low in glomeruli of patients with chronic renal disease. This may reflect a regulatory response to (inappropriately) high intrarenal angiotensin II concentrations.

Adult↗
PubMed1999

How can we improve prognosis in diabetic patients with end-stage renal disease?

Diabetes has become the single most important cause of end-stage renal failure, but survival of diabetic patients with renal replacement therapy continues to be poor. The major causes of death are cardiovascular complications. Most cardiovascular complications, particularly coronary atheroma, accumulate before patients enter renal replacement programs. This observation points to the need for improved patient care in pre-end-stage renal failure. In the diabetic patient, dialysis should be started earlier than in the nondiabetic patient, and prophylactic vascular access should be established when the glomerular filtration rate is approximately 20 ml/min. Proposals to improve prognosis of the diabetic patient with renal failure include interdisciplinary care for the patients with renal disease, strict normotension, administration of ACE inhibitors, administration of lipid-lowering agents, near-normalization of anemia using recombinant human erythropoietin, and improvement of diabetic foot care in the patient on renal replacement therapy.

Diabetic Nephropathies↗
PubMed1999

Genetic factors in IgA nephropathy.

Immunoglobulin A glomerulonephritis (IgA-GN) or Berger's disease is the most common glomerulonephritis when diagnosis is based on renal biopsy. The disease has a variable clinical course. Abnormalities in the production and/or catabolism of IgA are thought to play an important role in the etiology and pathogenesis of IgA-GN. Some evidence suggests that genetic factors determine the susceptibility to develop IgA-GN. Furthermore it has been proposed that genetic factors determine also the rate of progression. Since hypertension is an important predictor of progression, genes involved in blood pressure regulation have been analysed. A polymorphism in the gene for the angiotensin converting enzyme has been reported to be associated with progression. Further studies and progress in molecular biology will help to further elucidate the genetic factors which contribute to the development and progression of IgA-GN.

Biopsy↗
PubMed1999

Clinical features and natural history of IgA nephropathy.

IgA nephropathy (IgAN) is the most common form of glomerulonephritis worldwide. It is characterized by recurrent gross hematuria, microhematuria and/or proteinuria and diffuse mesangial IgA deposits in glomeruli. It is predominantly a disease of young males. Apart from primary IgAN (Berger's disease), IgA deposits in the glomeruli are also seen in Henoch-Schönlein purpura and in association with various of other diseases, particularly liver cirrhosis. Originally it was thought that IgAN was a benign disease, but it is now known that approximately 20-40% of patients develop progressive renal disease 5 to 25 years after diagnosis and progress to end-stage renal disease. Clinical predictors of progressive disease are elevated serum creatinine concentration at presentation, increased systemic blood pressure, persistent protein excretion > 1.0 g/day and histological predictors are glomerulosclerosis, tubular atrophy/interstitial fibrosis, extension of immune deposits to the perivascular space and crescent formation. Progression correlates more closely with the severity of tubulointerstitial lesions than with the degree of glomerular lesions. These features of IgAN reported in literature were mostly, but not completely, confirmed by analysis of all consecutive patients with biopsy proven IgAN and follow-up > 12 months in the renal units of Heidelberg and Prague using univariate analysis, multiple range test and multiple regression analysis.

Adult↗
PubMed1998

Diabetes--renal function--what are the special problems?

Diabetic nephropathy has become the single most important cause of endstage renal failure in most countries of the Western world. Against this background, the role of the renin-angiotensin system (RAS) and its blockade command considerable interest. In diabetic patients and in diabetic animals, the circulating components of the RAS are suppressed. Although the evidence is not completely uniform, there are indirect arguments (renal hemodynamic response to RAS blockade, AT1 receptor expression), however, which would be consistent with increased intrarenal action of angiotensin (ANG) II. There is solid evidence that ACE inhibitors effectively interfere with progression of micro-albuminuria both in IDDM and NIDDM. They also prevent progression of advanced renal failure in IDDM, while there is only preliminary evidence in this respect for NIDDM. ACE inhibitors are superior to conventional antihypertensive agents (with the possible exception of some calcium channel blockers), but such superiority is seen only when the levels of blood pressure are relatively high. In diabetic animals, treatment with ANG II receptor blockers interferes with the development of glomerular lesions. In acute and subacute studies on diabetic patients, ANG II receptor blockers reduced albuminuria (or proteinuria) more than beta-blockers. Head-on comparison of equipotent doses ACE inhibitors and ANG II receptor blockers in non-diabetic patients produced equal reductions in proteinuria. The long-term effects of ANG II receptor blockers on progression of advanced diabetic nephropathy is the object of two large international studies. The results will not be available before the year 2000.

Angiotensin Receptor Antagonists↗
PubMed1998

Association of a human G-protein beta3 subunit variant with hypertension.

Hypertension is a common disorder of multifactorial origin that constitutes a major risk factor for cardiovascular events such as stroke and myocardial infarction. Previous studies demonstrated an enhanced signal transduction via pertussis toxin-sensitive G proteins in lymphoblasts and fibroblasts from selected patients with essential hypertension. We have detected a novel polymorphism (C825T) in exon 10 of the gene encoding the beta3 subunit of heterotrimeric G proteins (GNB3). The T allele is associated with the occurrence of a splice variant, GNB3-s (encoding G beta3-s), in which the nucleotides 498-620 of exon 9 are deleted. This in-frame deletion causes the loss of 41 amino acids and one WD repeat domain of the G beta subunit. By western-blot analysis, G beta3-s appears to be predominantly expressed in cells from individuals carrying the T allele. Significant enhancement of stimulated GTPgammaS binding to Sf9 insect cells expressing G beta3-s together with G alpha(i)2 and G gamma5 indicates that this splice variant is biologically active. Genotype analysis of 427 normotensive and 426 hypertensive subjects suggests a significant association of the T allele with essential hypertension.

Alleles↗
PubMed1998

Smoking as a risk factor for end-stage renal failure in men with primary renal disease.

BACKGROUND: It is not known whether smoking increases the risk of end-stage renal failure (ESRF) in patients with primary renal disease. METHODS: We performed a retrospective multicenter case-control study including 582 patients from nine centers in Germany, Italy and Austria. The diseases investigated were IgA glomerulonephritis (IgA-GN) as a model of inflammatory renal disease and autosomal dominant polycystic kidney disease (ADPKD) as a model of non-inflammatory renal disease. Cases were patients who had progressed to ESRF and controls were patients who were not in ESRF, that is, whose serum-creatinine failed to progress to >3 mg/dl during the observation period and who did not require renal replacement therapy. Matching for renal disease (IgA-GN, ADPKD), gender, age at renal death and region of residence resulted in 102 individually matched pairs (IgA-GN N = 54, ADPKD N = 48). Multiple conditional logistic regression was used to estimate adjusted odds ratios for independent tobacco effects. RESULTS: In men (matched pairs: IgA-GN N = 44, ADPKD N = 28), a significant dose-dependent increase of the risk to progress to ESRF was found (non-adjusted). The baseline risk was defined as <5 pack-years (PY): (i) 5 to 15 PY, odds ratio 3.5 (95% CI 1.3 to 9.6), P = 0.017; (ii) >15 PY = 5.8 (2.0 to 17), P = 0.001. Systolic blood pressure, ACE inhibitor treatment and age at diagnosis emerged as potential confounders. After adjustment, the risk for ESRF in men with >5 PY was highly increased for patients without ACE inhibitor treatment [10.1 (2.3 to 45), P = 0.002] but not with ACE inhibitor treatment [1.4 (0.3 to 7.1), P = 0.65]. CONCLUSION: Smoking increases the risk of ESRF in men with inflammatory and non-inflammatory renal disease.

Adult↗
PubMed1998

Association of chronic kidney graft failure with recipient blood pressure. Collaborative Transplant Study.

Immunological rejection is the most important cause of kidney transplant failure. Recently, nonimmunological causes of long-term allograft failure have become more widely appreciated. In primary chronic renal disease, blood pressure is of overriding importance for long-term renal function. The role of blood pressure in determining long-term transplant outcome has not yet been established. We studied the influence of blood pressure post-transplantation on long-term kidney graft outcome in 29,751 patients. Outpatient blood pressure measurements were recorded and reported to the Collaborative Transplant Study. Graft and patient survival rates were analyzed over seven years in relation to blood pressure. Increased levels of systolic and diastolic blood pressure post-transplantation were associated with a graded increase of subsequent graft failure (P < 0.0001). Chronic graft failure was significantly associated with blood pressure even when patient death was censored (P < 0.0001). Cox regression analysis established increased blood pressure as an independent risk factor for graft failure. We conclude that post-transplant blood pressure is a highly significant predictor of long-term kidney graft outcome. Whether aggressive lowering of blood pressure improves long-term transplant outcome will have to be studied prospectively.

Blood Pressure↗
PubMed1998

Interaction of IGF-I and 1 alpha, 25(OH)2D3 on receptor expression and growth stimulation in rat growth plate chondrocytes.

Growth plate cartilage cell express receptors for, and are affected by both IGF-I and 1 alpha, 25(OH)2D3. The studies were undertaken to investigate interaction between these two hormone systems, that is, (i) to study effects of 1 alpha, 25(OH)2D3 on IGF-type 1 receptors (IGFIR), on IGF-I stimulated cell replication, colony formation, and on alkaline phosphatase activity (AP), and conversely, (ii) to study the effect of IGF-I on vitamin D receptor (VDR) expression on 1 alpha, 25(OH)2D3 stimulated growth parameters and on AP activity. Freshly isolated rat tibial chondrocytes were grown in monolayer cultures, (serum-free) or in agarose stabilized suspension cultures (0.1% FCS). Vitamin D receptor and IGFIR were visualized by immunostaining with the monoclonal antibody (mAb) 9A7 gamma and mAb alpha IR3, respectively, and quantitated by RT-PCR for mRNA and by Scatchard analysis using [3H]-1,25(OH)2D3 and [125I]-alpha IR3. Cell proliferation was measured by [3H]-thymidine incorporation, growth curves in monolayer cultures, and by colony formation in agarose-stabilized suspension cultures. IGF-I dose-dependently increased [3H]-thymidine incorporation. 1 alpha, 25(OH)2D3, but not 1 beta, 25(OH)2D3 was stimulatory at low ((10-12 M) and slightly inhibitory at high (10-8 M) concentrations. The effect of IGF-I was additive to that of 1 alpha, 25 (OH)2D3 [IGF-I 60 ng/ml, 181 +/- 12.7; 1 alpha, 25(OH)2D3 10(-12) M, 181 +/- 9.8%, IGF-I + 1 alpha, 25(OH)2D3, 247 +/- 16.7%, P < 0.05 by ANOVA] and specifically obliterated by polyclonal IGF-I antibody (AB-1). Interaction could also be confirmed in suspension cultures. IGFIR mRNA and [125I]-alphaIR3 binding was increased by low (10(-12) m) but not by high (10(-8) M) concentrations of 1 alpha, 25(OH)2D3. Homologous up-regulation by IGF-I (60 ng/ml) was specifically inhibited by AB-1 and markedly amplified by coincubation with 1 alpha, 25(OH)2D3 (10(-12)m). Immunostaining with alpha IR3 showed specific IGFIR expression in rat growth cartilage, but not liver tissue. Stimulation of chondrocytes with 1 alpha, 25(OH)2D3 or IGF-I suggested some increase of receptor expression in single cells, but the predominant effect was increased recruitment of receptor positive cells, Vitamin D receptor expression was markedly stimulated (fourfold) by IGF-I (60 ng/ml), but not IGF-II and inhibited by actinomycin D. This study shows that IGF-I and 1 alpha, 25(OH)2D3 mutually up-regulate their respective receptors in growth plate chondrocytes. In parallel, they have additive effects on cell proliferation and colony formation suggesting independent effector pathways.

Animals↗
PubMed1998

Insulin resistance and hyperinsulinemia are already present in patients with incipient renal disease.

In uremic patients resistance to the action of insulin has been documented, but it is not known at what stage of renal disease it appears. We therefore examined 29 patients with IgA glomerulonephritis (IgAGN) and 21 patients with adult polycystic kidney disease (ADPKD) in different stages of renal failure, and in addition, healthy age-matched subjects. Insulin sensitivity and other variables of glucose metabolism were assessed using a frequent sampling intravenous glucose tolerance test (minimal-model technique). Glomerular filtration rate (GFR) was assessed in renal patients using the inulin-clearance technique. Mean insulin sensitivity index (SI), that is, insulin sensitivity, was significantly lower (P < 0.001) in all patients combined than in matched healthy subjects (N = 16; 14 males, mean age 42 +/- 3 years; mean SI 8.6 +/- 0.8 min-1 uU/ml). The mean SI was not significantly different in patients with renal disease of immune (IgAGN) or non-immune (ADPKD) origin, and it was not correlated with GFR (r = 0.01, P < 0.52), intact PTH (r = -0.23, P < 0.11) or calcitriol concentration (r = -0.03, P < 0.82). Consequently, the mean SI was similar in renal patients with GFR within the normal range (N = 19; 17 males, mean age 41 +/- 2 years; mean GFR 119 +/- 5 ml/min/1.73 m2; 5.1 +/- 0.7 min-1 uU/ml), in patients with mild to moderate renal failure (N = 16; 15 males, 46 +/- 3 years; 67 +/- 4 ml/min/1.73 m2; 5.1 +/- 0.7 min-1 microU/ml) and in patients with advanced renal failure (N = 15; 13 males, 46 +/- 3 years; 25 +/- 2 ml/min/1.73 m2; 4.7 +/- 0.6 min-1 uU/ml). Mean fasted plasma insulin concentration, the area under the curve for plasma insulin concentration (AUC) and total insulin delivery (TID) during the glucose tolerance test were significantly higher in patients than in healthy subjects, reflecting hyperinsulinemia in renal patients. Further, fasted plasma insulin concentration (r = -0.32, P < 0.009), AUC (r = -0.62, P < 0.0001) and TID (r = -0.34, P < 0.004) in patients were significantly correlated with insulin sensitivity (SI). The present data document that insulin resistance and concomitant hyperinsulinemia are present early in the course of renal disease, that is, even in patients with GFR within the normal range, irrespective of the type of renal disease. This observation may have potential implications with respect to the high cardiovascular morbidity and mortality in patients with renal disease.

Adult↗
PubMed1998

Effect of 1,25 (OH)2 vitamin D3 on glomerulosclerosis in subtotally nephrectomized rats.

In the past, there has been considerable concern that treatment with active vitamin D might accelerate progression independent of hypercalcemia and hypercalcuria. Nevertheless, 1,25(OH)2D3 has known antiproliferative properties and has also been shown to inhibit renal growth. Since glomerular growth is a permissive factor for the development of glomerulosclerosis, we reasoned that 1,25(OH)2D3 might even attenuate progression. To test this working hypothesis we performed two experiments of 8 and 16 weeks duration, respectively, to compare subtotally nephrectomized (SNX) rats treated with ethanol and SNX treated with 1,25(OH)2D3. Control animals were sham operated and pair-fed with SNX animals. 1,25(OH)2D3 (3 ng/100 g body wt/day) was administered by osmotic minipump. 1,25(OH)2D3 had no significant effect on systolic blood pressure and only a transient effect on weight gain. SNX reduced the number of glomeruli (left kidney) from an average of 3.3 x 10(4) to 1.2 x 10(4) per kidney. Mean glomerular volume was 3.87 +/- 0.71 x 10(6) microns 3 in sham operated animals and significantly (P < 0.05) higher (10.1 +/- 1.75 x 10(6) microns 3) in untreated animals 16 weeks after SNX. Glomerular volume was significantly (P < 0.05) less in 1,25(OH)2D3 treated SNX [10.1 +/- 1.75 in ethanol vs. 7.04 +/- 1.78 in 1,25(OH)2D3 treated SNX]. In parallel, there was significantly (P < 0.01) less glomerulosclerosis [glomerulosclerosis index 1.16 +/- 0.14 in the ethanol treated SNX vs. 0.80 +/- 0.16 in SNX treated with 1,25(OH)2D3] in the eight week experiment. Albuminuria was significantly (P < 0.01) lower in 1,25(OH)2D3 treated than in ethanol treated SNX (mean 0.785 mg/24 hr, range 0.43 to 1.80, vs. 3.75 mg/24 hr, 1.29 to 14.2). The morphological data were directionally analogous in a second 16 week experiment. Only slight changes of the vascular sclerosis index and tubulointerstitial index were seen in SNX and were not affected by 1,25(OH)2D3 further. To prove that the effect of 1,25(OH)2D3 was independent of PTH, parathyreoidectomized SNX rats without or with 1,25(OH)2D3 treatment were examined seven days post-SNX. PCNA staining showed suppression of cell proliferation. Furthermore, in situ hybridization for transforming growth factor-B (TGF-beta) showed less vascular and tubular expression in 1,25(OH)2D3 treated rats. We conclude that 1,25(OH)2D3 has antiproliferative actions during the compensatory growth of nephrons in response to subtotal nephrectomy. These effects are independent of PTH. The data document that 1,25(OH)2D3 reduces renal cell proliferation and glomerular growth as well as glomerulosclerosis and albuminuria as indicators of progressive glomerular damage.

Animals↗